tbuckley/cabot-search huggingface dataset:
Moving From the Present to the Future—Elucidating the Association of Thyroid Dysfunction With Pregnancy Outcomes
Authors: Erik K. Alexander
Journal: JAMA Network Open (2022)

Ying Yang, MD, PhD; Tonglei Guo, MS; Jinrong Fu, MBBS; Jun Zhao, PhD; Yuanyuan Wang, MD, PhD; Yuan He, MD, PhD; Zuoqi Peng, BS; Ya Zhang, BS; Hongguang Zhang, BS; Yue Zhang, MS; Qiaomei Wang, MD; Haiping Shen, MD; Yiping Zhang, MD; Donghai Yan, MD; Xu Ma, MS; Haixia Guan, MD, PhD
Chimeric antigen receptor T cell therapy for cancer: clinical applications and practical considerations
Authors: Joseph E Maakaron, Marie Hu, Najla El Jurdi
Journal: BMJ (2022)

Abstract Chimeric antigen receptor T cells have revolutionized the treatment of hematological malignancies during the past five years, boasting impressive response rates and durable remissions for patients who previously had no viable options. In this review, we provide a brief historical overview of their development. We focus on the practical aspects of a patient’s journey through this treatment and the unique toxicities and current best practices to manage those. We then discuss the key registration trials that have led to approvals for the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL), diffuse large B cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma (MCL), and multiple myeloma. Finally, we consider the future development and research directions of this cutting edge therapy.
Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers
Authors: Tingting Gong, Weerachai Jaratlerdsiri, Jue Jiang, Cali Willet, Tracy Chew, Sean M. Patrick, Ruth J. Lyons, Anne-Maree Haynes, Gabriela Pasqualim, Ilma Simoni Brum, Phillip D. Stricker, Shingai B. A. Mutambirwa, Rosemarie Sadsad, Anthony T. Papenfuss, Riana M. S. Bornman, Eva K. F. Chan, Vanessa M. Hayes
Journal: Genome Medicine (2022)

Abstract Background African ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub-Saharan Africa are 2.5-fold greater than global averages. However, the region has largely been excluded from the benefits of whole genome interrogation studies. Additionally, while structural variation (SV) is highly prevalent, PCa genomic studies are still biased towards small variant interrogation. Methods Using whole genome sequencing and best practice workflows, we performed a comprehensive analysis of SVs for 180 (predominantly Gleason score ≥ 8) prostate tumours derived from 115 African, 61 European and four ancestrally admixed patients. We investigated the landscape and relationship of somatic SVs in driving ethnic disparity (African versus European), with a focus on African men from southern Africa. Results Duplication events showed the greatest ethnic disparity, with a 1.6- (relative frequency) to 2.5-fold (count) increase in African-derived tumours. Furthermore, we found duplication events to be associated with CDK12 inactivation and MYC copy number gain, and deletion events associated with SPOP mutation. Overall, African-derived tumours were 2-fold more likely to present with a hyper-SV subtype. In addition to hyper-duplication and deletion subtypes, we describe a new hyper-translocation subtype. While we confirm a lower TMPRSS2-ERG fusion-positive rate in tumours from African cases (10% versus 33%), novel African-specific PCa ETS family member and TMPRSS2 fusion partners were identified, including LINC01525, FBXO7 , GTF3C2 , NTNG1 and YPEL5 . Notably, we found 74 somatic SV hotspots impacting 18 new candidate driver genes, with CADM2 , LSAMP , PTPRD , PDE4D and PACRG having therapeutic implications for African patients. Conclusions In this first African-inclusive SV study for high-risk PCa, we demonstrate the power of SV interrogation for the identification of novel subtypes, oncogenic drivers and therapeutic targets. Identifying a novel spectrum of SVs in tumours derived from African patients provides a mechanism that may contribute, at least in part, to the observed ethnic disparity in advanced PCa presentation in men of African ancestry.
We Should Be Asking New Questions in Research on Weight Loss Surgery for Racial Minority Patients
Authors: Luise I. Pernar, Sherif Aly, Donald T. Hess
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Treatment With Topical Sirolimus for Recurrent Lymphatic Malformation of the External Urethral Meatus
Authors: Satoru Yonekura, Takaya Komori, Yoshihiro Ishida, Toshiaki Kogame, Kenji Kabashima
Journal: JAMA Dermatology (2022)

This case report describes a 17-year-old male patient with frog spawn–like vesicles around the urethra.
Association of 24-Hour Activity Pattern Phenotypes With Depression Symptoms and Cognitive Performance in Aging
Authors: Stephen F. Smagula, Gehui Zhang, Swathi Gujral, Naima Covassin, Jingen Li, Warren D. Taylor, Charles F. Reynolds, Robert T. Krafty
Journal: JAMA Psychiatry (2022)

Evidence regarding the nature and prevalence of 24-hour activity pattern phenotypes in older adults, especially those related to depression symptoms and cognition, is needed to guide the development of targeted mechanism research and behavioral interventions.To identify subgroups of older adults with similar 24-hour activity rhythm characteristics and characterize associated depression symptoms and cognitive performance.From January to March 2022, a cross-sectional analysis of the 2011-2014 National Health and Nutrition Examination and Survey (NHANES) accelerometer study was conducted. The NHANES used a multistage probability sample that was designed to be representative of noninstitutionalized adults in the US. The main analysis included participants 65 years or older who had accelerometer and depression measures weighted to represent approximately 32 million older adults.Latent profile analysis identified subgroups with similar 24-hour activity pattern characteristics as measured using extended-cosine and nonparametric methods.Covariate-adjusted sample-weighted regressions assessed associations of subgroup membership with (1) depression symptoms defined as 9-Item Patient Health Questionnaire (PHQ-9) scores of 10 or greater (PHQ-9) and (2) having at least psychometric mild cognitive impairment (p-MCI) defined as scoring less than 1 SD below the mean on a composite cognitive performance score.The actual clustering sample size was 1800 (weighted: mean [SD] age, 72.9 [7.3] years; 57% female participants). Clustering identified 4 subgroups: (1) 677 earlier rising/robust (37.6%), (2) 587 shorter active period/less modelable (32.6%), (3) 177 shorter active period/very weak (9.8%), and (4) 359 later settling/very weak (20.0%). The prevalence of a PHQ-9 score of 10 or greater differed significantly across groups (cluster 1, 3.5%; cluster 2, 4.7%; cluster 3, 7.5%; cluster 4, 9.0%; χ2﻿ P = .004). The prevalence of having at least p-MCI differed significantly across groups (cluster 1, 7.2%; cluster 2, 12.0%; cluster 3, 21.0%; cluster 4, 18.0%; χ2﻿ P &lt; .001). Five of 9 depression symptoms differed significantly across subgroups.In this cross-sectional study, findings indicate that approximately 1 in 5 older adults in the US may be classified in a subgroup with weak activity patterns and later settling, and approximately 1 in 10 may be classified in a subgroup with weak patterns and shorter active duration. Future research is needed to investigate the biologic processes related to these behavioral phenotypes, including why earlier and robust activity patterns appear protective, and whether modifying disrupted patterns improves outcomes.
Achieving Equitable Access to Acute Myocardial Infarction Therapies for Rural Patients—Is It Possible?
Authors: Eméfah C. Loccoh, Karen E. Joynt Maddox
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Costs, Reach, and Benefits of COVID-19 Pandemic Electronic Benefit Transfer and Grab-and-Go School Meals for Ensuring Youths’ Access to Food During School Closures
Authors: Erica L. Kenney, Lina Pinero Walkinshaw, Ye Shen, Sheila E. Fleischhacker, Jessica Jones-Smith, Sara N. Bleich, James W. Krieger
Journal: JAMA Network Open (2022)

<h3>Importance</h3> School meals are associated with improved nutrition and health for millions of US children, but school closures due to the COVID-19 pandemic disrupted children's access to school meals. Two policy approaches, the Pandemic Electronic Benefit Transfer (P-EBT) program, which provided the cash value of missed meals directly to families on debit-like cards to use for making food purchases, and the grab-and-go meals program, which offered prepared meals from school kitchens at community distribution points, were activated to replace missed meals for children from low-income families; however, the extent to which these programs reached those who needed them and the programs' costs were unknown. <h3>Objective</h3> To assess the proportion of eligible youths who were reached by P-EBT and grab-and-go meals, the amount of meals or benefits received, and the cost to implement each program. <h3>Design, Setting, and Participants</h3> This cross-sectional study was conducted from March to June 2020. The study population was all US youths younger than 19 years, including US youths aged 6 to 18 years who were eligible to receive free or reduced-price meals (primary analysis sample). <h3>Exposures</h3> Receipt of P-EBT or grab-and-go school meals. <h3>Main Outcomes and Measures</h3> The main outcomes were the percentage of youths reached by P-EBT and grab-and-go school meals, mean benefit received per recipient, and mean cost, including implementation costs and time costs to families per meal distributed. <h3>Results</h3> Among 30 million youths eligible for free or reduced-price meals, grab-and-go meals reached an estimated 8.0 million (27%) and P-EBT reached 26.9 million (89%). The grab-and-go school meals program distributed 429 million meals per month in spring 2020, and the P-EBT program distributed $3.2 billion in monthly cash benefits, equivalent to 1.1 billion meals. Among those receiving benefits, the mean monthly benefit was larger for grab-and-go school meals ($148; range across states, $44-$176) compared with P-EBT ($110; range across states, $55-$114). Costs per meal delivered were lower for P-EBT ($6.46; range across states, $6.41-$6.79) compared with grab-and-go school meals ($8.07; range across states, $2.97-$15.27). The P-EBT program had lower public sector implementation costs but higher uncompensated time costs to families (eg, preparation time for meals) compared with grab-and-go school meals. <h3>Conclusions and Relevance</h3> In this economic evaluation, both the P-EBT and grab-and-go school meal programs supported youths' access to food in complementary ways when US schools were closed during the COVID-19 pandemic from March to June 2020.
Assisted Reproductive Technology and Risk of Childhood Cancers
Authors: Shiue-Shan Weng, Yen-Tsung Huang, Yi-Ting Huang, Yi-Ping Li, Li-Yin Chien
Journal: JAMA Network Open (2022)

<h3>Importance</h3> The number of children born through the use of assisted reproductive technology (ART) has been increasing. These children may have higher risks for epigenetic alteration and adverse perinatal outcomes, which may be associated with childhood cancers. <h3>Objective</h3> To determine the associations between different modes of conception and childhood cancers and potential mediation by preterm birth and low birth weight. <h3>Design, Setting, and Participants</h3> This nationwide, population-based cohort study included registry data from 2 308 016 eligible parents-child triads in Taiwan from January 1, 2004, to December 31, 2017. A total of 1880 children with incident childhood cancer were identified. Data were analyzed between September 1, 2020, and June 30, 2022. <h3>Exposure</h3> Mode of conception, defined as (1) natural conception, (2) subfertility and non-ART (ie, infertility diagnosis but no ART-facilitated conception), or (3) ART (ie, infertility diagnosis and ART-facilitated conception). <h3>Main Outcomes and Measures</h3> Diagnosis of childhood cancer according to the<i>International Classification of Childhood Cancers, Third Edition</i>. <h3>Results</h3> The mean (SD) paternal and maternal ages were 33.28 (5.07) and 30.83 (4.56) years, respectively. Of the 2 308 016 children, 52.06% were boys, 8.16% were born preterm, and 7.38% had low birth weight. During 14.9 million person-years of follow-up (median, 6 years [IQR, 3-10 years]), ART conception was associated with an increased risk of any type of childhood cancers compared with natural conception (hazard ratio, 1.58; 95% CI, 1.17-2.12) and subfertility with non-ART conception (hazard ratio, 1.42; 95% CI, 1.04-1.95). The increased cancer risk of children conceived with ART was mainly owing to leukemia and hepatic tumor. The increased cancer risk associated with ART conception was not mediated by preterm birth or low birth weight. <h3>Conclusions and Relevance</h3> In this cohort study, children conceived via ART had a higher risk of childhood cancers than those conceived naturally and those born to parents with an infertility diagnosis did not use ART. The increased risk could not be explained by preterm birth or low birth weight.
Association of Preconception Thyrotropin Levels With Fecundability and Risk of Spontaneous Abortion in China
Authors: Ying Yang, Tonglei Guo, Jinrong Fu, Jun Zhao, Yuanyuan Wang, Yuan He, Zuoqi Peng, Ya Zhang, Hongguang Zhang, Yue Zhang, Qiaomei Wang, Haiping Shen, Yiping Zhang, Donghai Yan, Xu Ma, Haixia Guan
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Abundant evidence suggests thyroid dysfunction is associated with adverse pregnancy outcomes. However, associations of preconception thyrotropin levels outside of reference range with reproductive health outcomes are not well characterized. <h3>Objective</h3> To evaluate the associations of preconception thyrotropin levels with time to pregnancy (TTP) and risk of spontaneous abortion (SA). <h3>Design, Setting, and Participants</h3> This population-based cohort study used data from the Chinese National Free Prepregnancy Checkups Project. Female participants aged 20 to 49 years who were trying to conceive were enrolled between January 1, 2013, and December 31, 2016, for the analysis of TTP or SA. Data were analyzed between August 1, 2020, and July 5, 2021. <h3>Exposures</h3> Levels of thyrotropin within 1 year prior to pregnancy. <h3>Main Outcomes and Measures</h3> The main outcomes were TTP, assessed using hazard ratios (HRs), and SA, assessed using odds ratios (ORs), according to preconception thyrotropin levels. Thyrotropin dose-response associations were assessed using restricted cubic spline regression. <h3>Results</h3> Among 11 194 002 female participants (mean [SD] age, 27.56 [5.10] years) in the TTP cohort, 4 739 421 (42.34%) participants became pregnant within 1 year. Both low and high preconception thyrotropin levels were associated with delayed TTP compared with thyrotropin levels of 0.37 to 2.49 mIU/L (thyrotropin &lt;0.10 mIU/L: HR, 0.90; 95% CI, 0.89-0.92; thyrotropin 4.88-9.99 mIU/L: HR, 0.86; 95% CI, 0.86-0.87; thyrotropin ≥10.00 mIU/L: HR, 0.78; 95% CI, 0.77-0.79). In the SA analysis cohort including 4 678 679 pregnancies, 108 064 SA events (2.31%) were documented. High thyrotropin groups showed an increased risk of SA compared with the group with thyrotropin levels of 0.37 to 2.49 mIU/L (thyrotropin 4.88-9.99 mIU/L: OR, 1.33; 95% CI, 1.28-1.38; thyrotropin ≥10.00 mIU/L: OR, 1.25; 95% CI, 1.14-1.36). Preconception thyrotropin levels showed an inverted J-shaped dose-response association with TTP (χ<sup>2</sup> = 311.29; nonlinear<i>P</i> &lt; .001) and a J-shaped dose-response association with SA (χ<sup>2</sup> = 58.29; nonlinear<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> In this cohort study, preconception thyrotropin levels outside of reference range were associated with increased risk of reduced fecundity and SA. These findings may provide insights for the implementation of preconception thyroid function screening and the design of future levothyroxine supplementation trials.
Automated Office Blood Pressure Measurement Requires Technology and Implementation
Authors: Romsai Tony Boonyasai
Journal: JAMA Network Open (2022)

Thomas E. Kottke, MD, MSPH; Jeffrey P. Anderson, ScD, MPH; Jacob D. Zillhardt, MS; JoAnn M. Sperl-Hillen, MD; Patrick J. O’Connor, MD, MA, MPH; Beverly B. Green, MD, MPH; Rae Ann Williams, MD; Beth M. Averbeck, MD; Michael N. Stiffman, MD, MSPH; MarySue Beran, MD, MPH; Michael Rakotz, MD; Karen L. Margolis, MD, MPH
Refining Atrial Fibrillation Stroke Risk Estimates—A Call for Thoughtful Implementation Planning
Authors: Geoffrey D. Barnes
Journal: JAMA Network Open (2022)

Gregory Y. H. Lip, MD; Richard R. Murphy, MD; Farhad Sahiar, MD; Timothy J. Ingall, MD, PhD; Amol D. Dhamane, MS; Mauricio Ferri, MD; Patrick Hlavacek, MPH; Madison T. Preib, MPH; Allison Keshishian, MPH; Cristina Russ, MD; Lisa Rosenblatt, MD; Huseyin Yuce, PhD; Steven Deitelzweig, MD
Tetracyclines: four rings to rule infections through resistance and disease tolerance
Authors: Kátia Jesus, Luís F. Moita
Journal: Journal of Clinical Investigation (2022)

Several classes of antibiotics have long been known for protective properties that cannot be explained through their direct antimicrobial effects. However, the molecular bases of these beneficial roles have been elusive. In this issue of the JCI, Mottis et al. report that tetracyclines induced disease tolerance against influenza virus infection, expanding their protection potential beyond resistance and disease tolerance against bacterial infections. The authors dissociated tetracycline's disease-resistance properties from its disease-tolerance properties by identifying potent tetracycline derivatives with minimal antimicrobial activity but increased capacity to induce an adaptive mitochondrial stress response that initiated disease tolerance mechanisms. These findings have potential clinical applications in viral infections.
Sphingosine-1-phosphate receptor 1 activation in the central nervous system drives cisplatin-induced cognitive impairment
Authors: Silvia Squillace, Michael L. Niehoff, Timothy M. Doyle, Michael Green, Emanuela Esposito, Salvatore Cuzzocrea, Christopher K. Arnatt, Sarah Spiegel, Susan A. Farr, Daniela Salvemini
Journal: Journal of Clinical Investigation (2022)

Cancer-related cognitive impairment (CRCI) is a major neurotoxicity affecting more than 50% of cancer survivors. The underpinning mechanisms are mostly unknown, and there are no FDA-approved interventions. Sphingolipidomic analysis of mouse prefrontal cortex and hippocampus, key sites of cognitive function, revealed that cisplatin increased levels of the potent signaling molecule sphingosine-1-phosphate (S1P) and led to cognitive impairment. At the biochemical level, S1P induced mitochondrial dysfunction, activation of NOD-, LRR-, and pyrin domain-containing protein 3 inflammasomes, and increased IL-1β formation. These events were attenuated by systemic administration of the functional S1P receptor 1 (S1PR1) antagonist FTY720, which also attenuated cognitive impairment without adversely affecting locomotor activity. Similar attenuation was observed with ozanimod, another FDA-approved functional S1PR1 antagonist. Mice with astrocyte-specific deletion of S1pr1 lost their ability to respond to FTY720, implicating involvement of astrocytic S1PR1. Remarkably, our pharmacological and genetic approaches, coupled with computational modeling studies, revealed that cisplatin increased S1P production by activating TLR4. Collectively, our results identify the molecular mechanisms engaged by the S1P/S1PR1 axis in CRCI and establish S1PR1 antagonism as an approach to target CRCI with therapeutics that have fast-track clinical application.
Goblet cells need some stress
Authors: Malin E.V. Johansson, Gunnar C. Hansson
Journal: Journal of Clinical Investigation (2022)

The intestinal tract is protected by epithelium-covering mucus, which is constantly renewed by goblet cells, a specialized type of epithelial cell. Mucus is largely composed of MUC2 mucin, an enormous molecule that poses a high demand on the endoplasmic reticulum (ER) for proper folding and protein assembly, creating a challenge for the secretory machinery in goblet cells. In this issue of the JCI, Grey et al. reveal that the ER resident protein and folding sensor ERN2 (also known as IRE1β) was instrumental for goblet cells to produce sufficient amounts of mucus to form a protective mucus layer. In the absence of ERN2, mucus production was reduced, impairing the mucus barrier, which allowed bacteria to penetrate and cause an epithelial cell stress response. This study emphasizes the importance of a controlled unfolded protein response (UPR) for goblet cell secretion.